Subgroups of non-atypical hyperplasia of breast defined by proliferation of oestrogen receptor-positive cells

in normal breast, there is a negative association between expression of oes trogen receptor (ER) and the proliferation marker Ki67, indicating that ER- positive (ER +) cells do not divide, or that the receptor is down-regulated when they do so. However, dual staining has been found in carcinomas and p recancerous lesions, indicating that abnormal regulation of ER could be imp ortant in breast tumourigenesis. ER expression in relationship to cell prol iferation was studied in 241 foci of hyperplasia of usual type (HUT), a les ion associated with a 1.5 to 2-fold increase in risk of developing breast c ancer. Dual label immunofluorescence was employed, using the antibodies 1D5 and Ki67. Two hundred and thirteen foci of HUT contained ER + cells, which were distributed singly or contiguously and increased with age. Most foci resembled normal breast, but 51 contained dual labelled cells, which did no t increase with age. Some of these foci exhibited few, scattered ER; cells with greater proliferation rates than the ER-negative (ER-) cells, whereas others contained many, contiguous ER + cells, whose rate of proliferation w as less than that of the ER- cells. The latter picture is similar to that w hich has previously been reported in atypical ductal hyperplasia and ductal carcinoma in situ, The first type of HUT may evolve into the second. The p roportion of Ki67 + cells that was ER + was similar in both types, suggesti ng a homeostatic mechanism that slows the proliferation of ER + cells as th ey become confluent, Overriding this inhibition may be crucial in further p rogression. Non-atypical hyperplasia is thus heterogeneous in ER expression and proliferation and a significant proportion exhibit abnormal regulation of ER, These findings could have implications for pathological diagnosis, risk assessment, and prophylactic hormonal therapy, Copyright (C) 2000 John Wiley & Sons, Ltd.